Studies on the conversion of acetate, lactate, and malonate to succinate in the intact rat.

This investigation, preliminary reports on parts of which have previously appeared (1, 2), presents data on the conversion in the intact rat of the labeled carbon of the following compounds to succinate: NaHC*03, CH&*OOH, C*H&*OOH, CH&HOHC*OOH, and C*H&*HOHCOOH. All the animals were injected with malonate to augment the urinary excretion of succinate (3). The latter was isolated from the urine and degraded to determine the distribution of isotope in the succinate molecule. The conversion of carboxyl-labeled malonate to succinate was also studied. Information on the precursors of succinate in the intact animal or in relatively intact organs is meager (4). In the perfused hind limb of the rabbit, pyruvate administration has been reported to produce succinate accumulation (5). The administration of malonate, presumably because of its inhibition of succinic dehydrogenase, causes an excretion not only of succinate but also of cr-ketoglutarate and citrate (3, 6, 7), compounds which, according to the Krebs cycle, should be precursors of succinate proximal to the metabolic block.